In an untreated HIV infection, decreased CD4+ T-lymphocyte count is most likely caused by which immunologic mechanism?

• A. CD8+ T-lymphocyte-mediated killing
• B. Dendritic cell engulfment
• C. Destruction by reactive oxygen radicals
• D. Histamine-induced apoptosis

Answer: (A)

The key idea is that HIV-driven loss of CD4+ T cells mainly reflects immune-mediated destruction of those infected cells by cytotoxic CD8+ T lymphocytes. CD8+ T cells recognize HIV peptides presented on MHC class I on the surface of infected CD4+ T cells and kill them, reducing the CD4+ T-cell population. This cytotoxic T cell–mediated killing is the immune mechanism behind the depletion. CD8+ T cells are central to targeting infected cells, using perforin/granzyme or Fas-FasL pathways to induce apoptosis.

Dendritic cell engulfment is not the cause of CD4+ T-cell loss, and destruction by reactive oxygen radicals or histamine-induced apoptosis do not explain the selective depletion seen in untreated HIV.